It is well known to those skilled in the art of immunology that serum globulin fractions consisting of various antibody types such as IgA, IgM, and IgG, can be used to counter the corresponding antigens, thereby neutralizing the harmful effects of the antigens. The various antigens include carcinogenic, bacterial and viral species, and bioregulatory factors of plant and animal origin, as well as toxins and poisons.
Normally, upon exposure to a foreign antigen, the immune system of an animal will neutralize the bioregulatory and/or harmful effects of the antigen. The exposure of the immune system of a given mammal to foreign antigens can occur either naturally, or the host may be exposed to the antigen by the intentional administration of antigen in the form of a vaccine. When an animal is vaccinated with an antigenic substance, an immune response results in which the subject produces antibodies. This process is generally referred to as active immunization of the host species exposed to antigen. The antibodies produced by any given species of animal by the process of active immunization are homologous antibodies to said given species of animal.
It is well known that antibody produced in one species can be used to neutralize the effects of the corresponding antigen in other species. Passive immunization occurs when an individual from one species receives immune protection from antibodies produced in an individual of another species. This process requires the transfer of antibodies from a donor to a recipient. If the donor and recipient are of the same species the antibodies are homologous. On the other hand, if the donor and recipient are of different species, the antibodies are said to be heterologous.
Although it is known that passive immunization provides an effective method for the prevention and treatment of disease, the use of passive immunization in human medicine is limited because homologous human antibody formulations are not generally available. On the other hand, passive immunization of humans with heterologous antibodies produced in a donor animal species is employed only in situations of emergency because the use of heterologous antibodies can be dangerous. Examples of situations where heterologous antibodies are employed in human treatment include the use of snake venom and bee-venom antisera which are produced in horses. These antibodies neutralize the snake and bee toxins, thereby eliminating and/or reducing the harmful effects thereof.
Passive immunization of humans with heterologous antibodies is not safe because antibodies of non-human origin are foreign to the human immune system. Exposure of the recipient's immune system to the foreign donor antibody protein produces an immune reaction in the recipient against the foreign antibody. The immune response causes serum sickness, which can lead to anaphylactic shock and death. Therefore, despite the known and beneficial use of heterologous antibodies, this method of treatment is not generally employed because of safety considerations.
It is known that domestic avian species such as chickens, turkeys and ducks produce antibodies in the blood and eggs against factors which cause avian diseases, as well as against other antigens. For example, LeBacq-Verheyden, et al., Immunology, 27:683 (1974), and Nestle, G. A., et al., J. Med., 130:1337 (1969) have quantitatively analyzed immunoglobulins of the chicken. Polson, A., et al., Immunological Communications, 9:495-514 (1980), immunized hens against several proteins and natural mixtures of proteins, and detected IgY antibodies in the yolk of the eggs. Fertel, R., et al., Biochemical and Biophysical Research Communications, 102:1028-1033 (1981) immunized hens against prostaglandins and detected antibodies in the egg yolk. Jencenius, et al., Journal of Immunological Methods, 46:363-68 (1981) provide a method of isolating egg yolk IgG for use in immunodiagnostics. Polson, A., et al., Immunological Communications, 9:475-493 (1980) describe antibodies isolated from the yolk of hens that were immunized with a variety of plant viruses.
All of these references, however, relate only to studies of fowl immunoglobulins raised against various antigens, not all of them specifically affecting or causing mammalian diseases or conditions. As noted, Polson (both papers, 1980) or Jencenius supra, suggest the use of avian antibodies instead of mammalian antibodies as tools in diagnostic procedures. Polson, Immunological Communications, 475-493 (1980) suggests, on page 491, that it might be possible to protect newly hatched chickens passively against diseases to which their mothers were not exposed by injection of the chicks with yolk IgY derived from hens that were hyperimmunized against the diseases. This suggestion, in addition to being speculative, deals solely with homologous passive immunization of one species with the antibody obtained from the same species, albeit, a different individual.
Jencenius, et al., Journal of Immunological Methods 46, supra, states at page 67 that "one may even speculate that, by providing large amounts of neatly wrapped antibody, eggs from suitable immunized chickens might be a useful and harmless therapy for some intestinal infections, if steps can be taken to minimize the degradation of the antibody by intestinal proteolytic enzymes." The authors analogize this to the idea of treating infections with milk from immunized animals, citing the work of Campbell, et al., Journal of Immune Milk, 1:3 (1964). The suggestion in Jencenius et al., is, by its own admission, speculative. In addition, it is accompanied by the warning that the antibody would be degraded by intestinal proteolytic enzymes.
The phylogenetic distance between birds and mammals have made the chicken and other domesticated fowl an illogical choice for producing antibodies against mammalian diseases or conditions. The obvious choice of antibodies for immune therapeutic products intended for the treatment of mammalian species has been another mammal having a close biogenetic relationship. For example, it would not be logical to treat human subjects with chicken antibody administered in a parenteral dose formulation, because chicken protein is foreign to the human immune system, and would cause allergic reactions with repeated use. Indeed, there is no evidence in the scientific literature that antibodies derived from bird eggs have been used in preventing or treating conditions in mammals.